POS0845 EFFECTS OF NINTEDANIB ON CIRCULATING BIOMARKERS IN PATIENTS WITH PROGRESSIVE FIBROSING AUTOIMMUNE DISEASE-RELATED INTERSTITIAL LUNG DISEASES
Authors: T. Maher, F. Bonella, S. Assassi, I. Noth, C. Diefenbach, C. Ittrich, K. Rohr, M. Kolb
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Data from the randomised placebo-controlled INBUILD trial in subjects with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis suggested that nintedanib may have effects on circulating levels of biomarkers of epithelial injury, inflammation and extracellular matrix (ECM) turnover. <h3>Objectives</h3> We investigated the effects of nintedanib on circulating biomarkers in subjects in the INBUILD trial who had pulmonary fibrosis due to autoimmune disease. <h3>Methods</h3> Subjects in the INBUILD trial had diffuse fibrosing ILD of &gt;10% extent on HRCT and met criteria for progression of ILD within the prior 24 months, despite management in clinical practice. Subjects were randomised to receive nintedanib or placebo, stratified by fibrotic pattern on HRCT (usual interstitial pneumonia-like fibrotic pattern or other fibrotic patterns). Blood samples were taken at baseline and at weeks 12, 24, 36 and 52. Fold changes in adjusted mean levels of biomarkers were analysed using a linear mixed model for repeated measures. Data were log10 transformed before analysis and estimates of change from baseline were back-transformed. <h3>Results</h3> Of 663 subjects, 170 had autoimmune disease-related ILDs; 82 of these subjects received nintedanib and 88 received placebo. Over 52 weeks, there were treatment-related decreases in fold changes from baseline in levels of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), CA-125 (markers of epithelial injury) in subjects who received nintedanib versus placebo (Figure 1). The most pronounced difference between nintedanib and placebo was in CA-125. The effect of nintedanib on CA-125 was observed as early as week 12. Small decreases in fold changes from baseline in soluble intercellular adhesion molecule (s-ICAM) (a marker of inflammation) and in C3M and pro-C6 (markers of ECM turnover) were observed in subjects who received nintedanib versus placebo (Figure). No notable trends were observed for the other biomarkers assessed. <h3>Conclusion</h3> In subjects with progressive fibrosing autoimmune disease-related ILDs, nintedanib reduced circulating levels of markers of epithelial injury, with the most pronounced effect observed on CA-125. The treatment-related decreases in these markers in subjects with autoimmune disease-related ILDs were similar to those observed in subjects with other ILDs. <h3>Acknowledgements</h3> The INBUILD trial was funded by Boehringer Ingelheim. Martin Kolb was a member of the INBUILD Steering Committee. <h3>Disclosure of Interests</h3> Toby Maher Speakers bureau: Boehringer Ingelheim, Roche/Genentech, United Therapeutics, Consultant of: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, MSD, Roche/Genentech, United Therapeutics, UCB, Grant/research support from: AstraZeneca, GlaxoSmithKline, UCB, Francesco Bonella Speakers bureau: Boehringer Ingelheim, Roche, Sanofi, Consultant of: Boehringer Ingelheim, Roche, Sanofi, Shervin Assassi Speakers bureau: Integrity Continuing Education, Consultant of: Abbvie, AstraZeneca, aTyR, Boehringer Ingelheim, CSL Behring, TeneoFour, Grant/research support from: Boehringer Ingelheim, Janssen, Momenta, Imre Noth Consultant of: Boehringer Ingelheim, Genentech, Sanofi, Grant/research support from: Veracyte, Claudia Diefenbach Employee of: Boehringer Ingelheim, Carina Ittrich Employee of: Boehringer Ingelheim, Klaus Rohr Employee of: Boehringer Ingelheim, Martin Kolb Speakers bureau: Boehringer Ingelheim, Roche, Consultant of: Abbvie, Algernon Pharmaceuticals, Bellerophon Therapeutics, Boehringer Ingelheim, CSL Behring, DevPro Biopharma, Horizon Therapeutics, LabCorp, MitoImmune Therapeutics, Nitto Denko, Pieris Pharmaceuticals, Roche, ShouTi, United Therapeutics, Grant/research support from: Boehringer Ingelheim, Pieris Pharmaceuticals, Roche, ShouTi.